HMGB factors are required for posterior digit development through integrating signaling pathway activities
Copyright policy )HMGB factors are required for posterior digit development through integrating signaling pathway activities
AbstractThe chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.5, Hmgb1−/−; Hmgb2+/− embryos exhibit a loss of digit5, the most posterior digit, in the forelimb. We show that Hmgb1−/−; Hmgb2+/− forelimbs have a reduced level of Shh signaling, as well as a clear downregulation of Wnt and BMP target genes in the posterior region. Moreover, we demonstrate that hmgb1 and hmgb2 in zebrafish embryos enhance Wnt signaling in a variety of tissues, and that double knockdown embryos have reduced Wnt signaling and shh expression in pectoral fin buds. Our data show that Hmgb1 and Hmgb2 function redundantly to enhance Wnt signaling in embryos, and further suggest that integrating Wnt, Shh, and BMP signaling regulates the development of digit5 in forelimbs. Developmental Dynamics 240:1151–1162, 2011. © 2011 Wiley‐Liss, Inc.
- University of Minnesota System United States
- Scripps Research Institute United States
- Japan Health & Research Institute Japan
- University of Minnesota Morris United States
- University of Minnesota United States
Gene Expression Regulation, Developmental, Extremities, Embryo, Mammalian, Immunohistochemistry, Models, Biological, Mice, Mutant Strains, Wnt Proteins, Mice, Pregnancy, HMGB Proteins, Bone Morphogenetic Proteins, Animals, HMGB2 Protein, Female, Hedgehog Proteins, HMGB1 Protein, In Situ Hybridization, Zebrafish, Signal Transduction
Gene Expression Regulation, Developmental, Extremities, Embryo, Mammalian, Immunohistochemistry, Models, Biological, Mice, Mutant Strains, Wnt Proteins, Mice, Pregnancy, HMGB Proteins, Bone Morphogenetic Proteins, Animals, HMGB2 Protein, Female, Hedgehog Proteins, HMGB1 Protein, In Situ Hybridization, Zebrafish, Signal Transduction
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